HHS Releases 2016 PHEMCE Strategy and Implementation Plan

The 2016 Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Strategy and Implementation Plan (SIP), released this week by the U.S. Department of Health and Human Services, describes the priorities that HHS, in collaboration with its interagency partners, will implement over the next five years.

The 2016 PHEMCE SIP updates the 2014/2015 PHEMCE SIPs and provides the blueprint for the PHEMCE to enhance national health security through the development, procurement and planning for effective use of critical medical countermeasures.

Information regarding the use of funds and authorities originally authorized and provided by the Project BioShield Act of 2004

Editor’s Note: Here we highlight some of the major federal investments in medical countermeasures, and provide snapshots of important summary information in the report. Please access the report for full context: 2016 PHEMCE Strategy and Implementation Plan (SIP)

In the near- and mid-terms, ASPR, working with subject matter experts from across the PHEMCE, will develop or update specific MCM requirement documents including those listed here.

MCM requirement documents (con't)

Through FY 2020, NIH will emphasize the early-stage research programs listed in Table 4.

Early-stage products that demonstrate promise for advanced development will be brought to the attention of BARDA through regular communications and opportunities for technology transfer.

Contracts awarded for the development of antiviral therapeutics included host-targeting antiviral compounds for treatment of influenza (Kineta, Inc.) and Ebola and Marburg infections (Southwest Research Institute), and a contract for the development of RNA polymerase inhibitors for treatment of chikungunya and related viral infections (Emory University).

In 2016, NIAID initiated support for a Phase 1 clinical study of the antibacterial therapeutic TP-271 (CUBRC, Inc. and Tetraphase, Inc.), which is a novel tetracycline-based derivative.

In 2015, NIAID made 14 awards for the discovery and early stage development of new antibacterial products under Request for Assistance (RFA) -14-026, Development of Novel Therapeutics for Select Pathogens, which focused in part on new therapeutics for Gram-negative pathogens. Many of these projects are focused on novel strategies to combat antibacterial resistance, such as anti-virulence, immune-based therapies, adjunctive therapies and biofilm inhibitors.

NIAID continues to support the development of novel vaccine candidates, which target biodefense and emerging infectious disease pathogens, that include novel technologies/platforms that accelerate the immune response, improve ease of delivery, or enhance stability. These vaccine candidates also have the potential to provide protection when used for PEP in health care workers and the local population in outbreak scenarios.

Several vaccines focus on technologies that accelerate the immune response and/or improve ease of delivery. These include four anthrax vaccines, a saponin-based recombinant protective antigen (rPA) vaccine (Fraunhofer), intranasal rPA vaccine formulated in nanoemulsion adjuvant W805EC (Public Health England and NanoBio), adjuvanted rPA vaccine delivered by a Solid Dose Injection (SDI) system (Pfenex), and an oral adenovirus serotype 4 (Ad4) vaccine vector expressing rPA (PaxVax). Other candidates focus on formulations that enhance stability and include two anthrax vaccines, a lyophilized formulation of AV7909 (Emergent) and a lyophilized rPA vaccine (PharmAthene). The purpose of these efforts is to evaluate the technologies (e.g., adjuvants, delivery system, and dry formulations) that may have applicability to multiple threat areas.

In the near- and mid-terms, multiple candidates for next-generation anthrax vaccines or botulinum antitoxins, broad-spectrum antimicrobials, and influenza antivirals may be available for advanced development consideration.

In 2015, NIH released a broad agency announcement (BAA) entitled “Development of Therapeutic Medical Countermeasures for Biodefense and Emerging Infectious Diseases” with awards scheduled for FY 2016. The disease focus for these two BAA efforts is biodefense and emerging infectious diseases with particular interest in broad-spectrum antibiotics addressing antimicrobial resistance, as well as broad-spectrum antivirals and small molecule antitoxins.

NIH will continue to manage the CAP to create and coordinate teams of scientific, medical, and product development experts to guide investigators working on multi-use products for biodefense, drug resistance, and emerging disease applications. The CAP was initiated as a result of the 2010 PHEMCE Review to accelerate the development of promising, high-priority MCMs and is focused on the early phase of transitioning basic research discoveries and early phase translational concepts into promising preclinical candidates. Five of nine Ebola vaccine candidates to enter human clinical testing have been shepherded by CAP.

NIH’s long-term focus (FY 2021 and beyond) will increase the emphasis on platform technologies that either allow for the development of broad-spectrum MCMs or permit more rapid development of agent-specific MCMs. Additionally, NIH will focus on MCMs with commercial applicability for routine (non-emergency) public health diseases of both domestic and international significance.

BARDA Medical Countermeasure Investments

In FY 2015, BARDA continued to work closely with NIH and DoD to monitor the progress of programs supported under research and development and transition promising candidates. In FY 2015, BARDA re-issued the three BAAs to support advanced development of CBRN and Influenza MCMs and the BAA for Innovations. They were modified to align with the 2015 PHEMCE SIP and to address remaining gaps in preparedness as well as address new initiatives such as CARB and EID.

In addition, BARDA made new awards under the Nonclinical Services Network to bring on new performers to address chemical and radiation and nuclear threats and anticipates new awards in FY 2016-17 to continue to support biothreats.

BARDA is currently supporting a robust pipeline of approximately 65 candidate products under ARD. The information below highlights some of the successes in FY 2015.

Anthrax Vaccines and Antitoxins

BARDA, along with PHEMCE partners supported the approval of BioThrax® for the PEP indication (licensed November 2015). BARDA and NIAID completed a clinical study evaluating reduced doses of BioThrax® that may inform the use of this vaccine during an emergency. BARDA continues to support expansion of domestic manufacturing of the currently licensed vaccine and anticipates approval of the facility in FY 2016.

BARDA continues to support development of an enhanced BioThrax® formulation that contains an adjuvant. BARDA has transitioned one of the rPA based anthrax vaccine candidates to clinical evaluation. Finally, BARDA is supporting the development of a transformative anthrax vaccine candidate that may provide protection in a single dose that is administered nasally.

Anthrax immune globulin (manufactured by Cangene/Emergent) was licensed by the FDA in March 2015 and ETI-204 (Anthim, manufactured by Elusys) was licensed in March 2016.

Broad Spectrum Antimicrobials and CARB

BARDA is currently supporting six programs; two of the programs are portfolios of candidates under OTAs. Two of the companies BARDA is supporting have completed their registrational Phase 3 trials and BARDA anticipates new drug application (NDA) submissions in FY 2016. BARDA is supporting one of the companies, Cempra, to conduct a pediatric trial.

Smallpox Vaccine and Antivirals

BARDA continues to support one smallpox vaccine for at-risk individuals and two smallpox antiviral candidates. Bavarian Nordic (BN) continues to work toward licensure of its smallpox vaccine MVA. It has met its primary and secondary endpoints in one of its Phase 3 trials and continues to enroll in its pivotal Phase 3 trial comparing MVA to ACAM2000.

BARDA and PHEMCE partners continue to work with BN to transition the current stockpile of liquid frozen product to a lyophilized formulation. BN has shown non-inferiority in a Phase 2 clinical study and non-clinical studies comparing the liquid frozen to the lyophilized formulation. BARDA made initial procurements of bulk MVA in FY 2015 and anticipates additional procurement of bulk in FY 2016 to complete the transition to this improved formulation of the vaccine.

SIGA continues to develop TPOXX (ST-246) under both PBS and ARD contracts. BARDA anticipates it moving forward with its pivotal Phase 3 study in FY 2016. Chimerix continues to develop brincidofovir and has shown efficacy in non-clinical studies and continues to pursue its commercial indications for cytomegalovirus (CMV) and adenovirus infections.

Burn Programs

BARDA continues to support a portfolio of programs to address the continuum of care for burn patients: both field applications and definitive care. BARDA added one new program, PolyNovo, to the portfolio in FY 2015. In addition, four programs were transitioned or added under PBS. These include: a silver impregnated field dressing, an enzymatic debridement technology, a cell-based skin substitute, and donor tissue sparing technology. The products can be used in concert to improve the care and outcome of individuals with burn injuries.

Radiation and Nuclear

BARDA continues to support multiple candidates to address the various subsyndromes resulting from exposure to ionizing radiation or radiological dispersal. In March of 2015, based in part on NIAID-funded preclinical studies, FDA approved a new indication for Neupogen®, to increase survival in adult and pediatric patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome, H-ARS). This program has been supported by the PHEMCE partners and has been purchased under PBS since 2013 and maintained under vender managed inventory.

In November of 2015, FDA approved Neulasta® for H-ARS, based in part on preclinical studies funded by the NIAID.

BARDA is working with colleagues at the FDA to develop models for hematopoietic and gastro-intestinal injury using the minipig. Together, the goal is to establish models that will stand up to regulatory rigor and support the approval of candidate products.

BARDA is also reaching out to large pharmaceutical companies to evaluate already approved products or those under development to determine their potential efficacy to address the various sub-syndromes resulting from acute radiation exposure. One example is that BARDA is working with Johnson & Johnson under a material transfer agreement to evaluate its thrombopoietin mimetic to address vascular injury that results from acute exposure to ionizing radiation. NIAID is also working with several companies on the development of thrombopoietin mimetics.

Chemical

BARDA continues to support the University of Hertfordshire to develop improved decontamination guidance for first responders.

BARDA has held multiple end user engagements and field exercises with state and local officials to develop this improved guidance. The initial guidance was released, Primary Response Incident Scene Management (PRISM) series,68 and BARDA will continue to refine this guidance. BARDA made a new award to the University of Colorado, which is working with Genentech to evaluate its product, tPA, for lung injury resulting from exposure to chlorine. BARDA is reaching out to large pharmaceutical companies to evaluate already approved products or those under development to determine their potential to address injuries resulting from exposure to chemical agents.

Biodosimetry and Biodiagnostics

BARDA continues to support a portfolio of diagnostic tests both for point-of-care and automated laboratory settings to determine the absorbed dose of ionizing radiation an individual may have received. BARDA anticipates successful programs to transition to PBS in FY 2016-17. BARDA has also made awards to support platform technologies for biodiagnostics to address multiple bacterial pathogens.

Ebola Response

BARDA went from supporting a single Ebola therapeutic in FY 2014 to supporting several therapeutic candidates in FY 2015. BARDA’s current plans to develop MCMs to address Ebola are addressed in greater detail in the Ebola Preparedness and Response section of this report.

These include continued support of Mapp Bio (ZMapp), BioCryst (BCX4430), and Regeneron (REGN3479-70-71); support for non-clinical, manufacturing, and clinical studies; under the Centers for Innovation in Advanced Development and Manufacturing (CIADM), a partnership with Genentech to evaluate their humanized versions of ZMapp; and efforts with Medicago and Fraunhofer to evaluate expression of ZMapp in other tobacco based plant systems.

Finally, BARDA employed the National Medical Countermeasures Response Infrastructure (core services) to: support fill/finish and manufacturing of Ebola therapeutics; evaluate therapeutics under the Nonclinical Development Network; assist companies by providing regulatory support when filing INDs; support the clinical research organization to support the CDC sponsored STRIVE study in Sierra Leone under the Clinical Studies Network; use of the CIADMs to manufacture an Ebola therapeutic; and lead efforts for modeling of the Ebola outbreak through BARDA’s Analytic Decision Support Division.